The theoretical construct of resilience, better-than-expected outcome following potential risk, provides an innovative framework for the longitudinal study of intrauterine cocaine exposure (IUCE) & intrauterine substance exposure (IUSE). Resilience evolves from person/environment interactions, which may buffer the impact of biologic & social risks. We propose a masked multidisciplinary longitudinal follow-up of 140-150 urban primarily African American/African Caribbean participants aged 18-24 (50% with IUCE), continuously followed since birth to document risks, protective & promotive factors in multiple domains. Unique features of the already collected & proposed data set include: Ainsworth attachment classification at 12 months, repeated prospective measurement since infancy of the caregiver's & child's exposure to violence, repeated measures of material hardship, & parents' incarceration, with the addition in this cycle of measures of discrimination, positive ethnic identity, & quality of young adult intimate relationships 61% of the sample initiated substance use by age 16 by self-report or urine assay. During the proposed period of study (4/1/2010 - 3/31/2015) the participants enter the developmental epoch when the emergence of SUDs, possible recovery from such disorders, & ability to undertake early adult roles become measurable, & executive & memory functions mature. We focus on selected biological contextual factors, which may be crucial in determining resilience & risk in these domains. We consider as potential biologic factors among others: gender, birth weight, IUCE, age at assessment, & a novel composite measurement of overall level of intrauterine substance exposures (IUSE) including levels of cocaine, tobacco, alcohol, & marijuana in a single scale, as well as the individual substances as distinct variables. The participant's timing of initiation & concurrent level of adolescent / young adult use of psychoactive substances are both indicators of biologic risk to the still developing central nervous system & a major outcome. We will analyze the influence of potentially buffering contextual factors from infancy to young adulthood contributing to: 1) Freedom from SUDs; 2) Greater adaptive role function including fewer HIV risk behaviors, later childbearing, fewer psychiatric symptoms, less criminal behavior, & positive adaptation in education, employment & personal relationships; & 3) Expected maturation of executive & memory functions. We propose generalized mixed linear models to utilize fully the longitudinal nature of the data, including growth curve models to delineate trajectories, stratified & interaction models to examine moderators, & structural equation path models to evaluate mediation. IUSE impacts many Americans of all ethnic groups ranging from infants to adults. This sample represents a demographic, which, compared to other groups, suffers more adverse life consequences from substance use & which, with or without IUSE, faces disproportionate levels of community stressors. Identification of factors fostering resilience in this context of health disparities is of particular scientific & public health relevance. PUBLIC HEALTH RELEVANCE: Many Americans, ranging from infants to adults, have experienced intrauterine exposures to psychoactive substances which may put them at increased risk of adverse life trajectories in many dimensions. Therefore, following intrauterine exposures, delineation of infant, childhood, adolescent, and concurrent factors which can promote or inhibit resilience during young adulthood in multiple domains (including freedom from substance use disorders) has important implications for public health interventions.